There are a multitude of drug delivery methods. Most current methods of drug delivery entail an initial delivery through oral ingestion, inhalation, transmucosal absorption, intravascular injection or intravenous modalities. Some drugs can now be delivered with new technologies, including iontophoresis, ultra-sound and transdermal patches. The most recent advancements have been with targeted drug delivery modalities wherein a targeted release system releases the drug in a dosage form, thereby targeting a localized disease area and reducing the amount of drug taken by the patient. The use of nanoparticles is expected to have a major impact on drug delivery because this small size enables deep access to cells. These new technologies, which provide the initial entry of drugs into the body, have created numerous patient benefits, but there are still opportunities for other types of non-invasive drug delivery techniques. Delivery of drugs that provide effective therapeutic concentrations to targeted tissues, with minimal side effects, is a major challenge because of physiological and anatomical barriers. As an example, the eye is uniquely protected with an epithelial membrane to prevent the entry of foreign bodies such as bacteria from entering the eye socket. In addition, there is a blood barrier surrounding the eye which prevents the migration of molecules from other parts of the body into the eye, whether such molecules comprise diseases or are disease treating entities. As a result of this natural protection, the eye can be extremely difficult to treat. Typically, therapeutic drugs needed for treatment of serious ocular adverse conditions or diseases are delivered with needle injection. This technique poses some risk to the patient, especially when it is necessary to perform multiple injections, such as injecting the drug Avastin into the vitreous for treatment of age-related macular degeneration.
Another type of ophthalmic drug delivery, which is painful to the patient and can sometimes lead to eye infections, is the delivery of drug directly into the cornea. Currently, this procedure normally requires surgical removal of the epithelium. This invasive method is typically used for the delivery of riboflavin into the cornea for purposes of crosslinking corneal collagen tissue. After removing the epithelium, drops of the riboflavin are placed on the corneal surface over a period of time to allow the riboflavin to soak into the corneal tissue. Upon exposure to UVA light, the riboflavin serves as a photosensitizer to create new covalent crosslinks between collagen strands to increase corneal stiffness. Typically it takes 3 to 5 days for re-growth of the epithelium and infections can occur during this period. Moreover, the recovery period is painful to the patient, and there is also risk of haze and scar formation. Despite the fact that corneal collagen crosslinking can be associated with a painful recovery process, it has been clinically proven to manage ectatic corneal disorders such as keratoconus by halting their progression.
Besides ectatic corneal disorders in the anterior segment of the eye, there are numerous other pathological conditions, such as keratoconjunctivitis sicca (KCS), glaucoma, and anterior uveitis which require treatment. KCS, also known as dry eye, is an eye condition caused by inflammation of the cornea and conjunctiva resulting from lack of tear production, causing dryness and pain in those tissues. The KCS condition causes ocular irritation, loss of vision, ocular surface diseases, and the risk of corneal ulceration. Dry eye affects between 10-15% of the US population and is treated primarily with topical drop instillation. However, less than 10% of the instilled eye drop dose is retained on the ocular surface.
Consequently, a drug delivery procedure is needed for the eye, which can: 1) deliver drug quickly and painlessly to the treatment area; 2) do so in a minimally invasive manner, that is, without disrupting the epithelium and 3) improve the residence time for the drug. Such a drug delivery procedure may provide significant medical benefit for patients.
Beyond the need for delivery of drugs into the eye, a significant need also exists for minimally invasive delivery of drugs to other parts of the body. Oral ingestion and injection of drugs, with their respective systemic side effects, are not always safe and practical. For example, a significant obstacle to dermal and transdermal drug delivery is the resilient barrier that the epidermal layers of the skin, primarily the stratum corneum, presents for the diffusion of exogenous chemical agents. Another challenge is the delivery of various therapeutic agents deeper within the skin, such as into the sudoriferous and sebaceous glands or at the base of hair follicles. Further advancement of transdermal drug delivery requires the development of novel delivery systems that are suitable for modern, macromolecular protein and nucleotide therapeutic agents.
The choice regarding a drug delivery modality is dependent on several factors, including the active substance in question, its pharmacokinetic profile, and the desired location of therapeutic action. Having the ability to target a specific location in the body such that a drug is active primarily in the target area, is the ultimate goal of a drug delivery system.
The main advantages of delivering drugs topically include the elimination of first-pass metabolism, sustained drug delivery, reduced frequency of administration, reduced side effects, and improved patient compliance. However, very few drugs are suitable for topical delivery, with passive penetration through skin normally being limited to small molecules (<500 Da), which are neutral and relatively lipophilic. More recently, nanomaterials are increasingly being exploited as carriers to deliver drugs or gene fragments to specific cell targets for therapeutic purposes.
The current invention addresses the need for non-invasive administration of therapeutic agents to a variety of targets including, but not limited to, transdermal administration to the skin and, in particular, topical administration to the epithelium of the eye.